The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer
Summary: The approval of the first kinase inhibitor, Gleevec, ushered in a paradigm shift for oncological treatment—the use of genomic data for targeted, efficacious therapies. Since then, over 48 additional small-molecule kinase inhibitors have been approved, solidifying the case for kinases as a h...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-10-01
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| Series: | Cell Reports Medicine |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666379120301701 |
| _version_ | 1818257337721290752 |
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| author | Derek Essegian Rimpi Khurana Vasileios Stathias Stephan C. Schürer |
| author_facet | Derek Essegian Rimpi Khurana Vasileios Stathias Stephan C. Schürer |
| author_sort | Derek Essegian |
| collection | DOAJ |
| description | Summary: The approval of the first kinase inhibitor, Gleevec, ushered in a paradigm shift for oncological treatment—the use of genomic data for targeted, efficacious therapies. Since then, over 48 additional small-molecule kinase inhibitors have been approved, solidifying the case for kinases as a highly druggable and attractive target class. Despite the role deregulated kinase activity plays in cancer, only 8% of the kinome has been effectively “drugged.” Moreover, 24% of the 634 human kinases are understudied. We have developed a comprehensive scoring system that utilizes differential gene expression, pathological parameters, overall survival, and mutational hotspot analysis to rank and prioritize clinically relevant kinases across 17 solid tumor cancers from The Cancer Genome Atlas. We have developed the clinical kinase index (CKI) app (http://cki.ccs.miami.edu) to facilitate interactive analysis of all kinases in each cancer. Collectively, we report that understudied kinases have potential clinical value as biomarkers or drug targets that warrant further study. |
| first_indexed | 2024-12-12T17:42:03Z |
| format | Article |
| id | doaj.art-9611c9d86241428792ddeb70ba9b8b13 |
| institution | Directory Open Access Journal |
| issn | 2666-3791 |
| language | English |
| last_indexed | 2024-12-12T17:42:03Z |
| publishDate | 2020-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports Medicine |
| spelling | doaj.art-9611c9d86241428792ddeb70ba9b8b132022-12-22T00:17:02ZengElsevierCell Reports Medicine2666-37912020-10-0117100128The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of CancerDerek Essegian0Rimpi Khurana1Vasileios Stathias2Stephan C. Schürer3Department of Pharmacology, Miller School of Medicine, University of Miami, Miami, USADepartment of Pharmacology, Miller School of Medicine, University of Miami, Miami, USADepartment of Pharmacology, Miller School of Medicine, University of Miami, Miami, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, USADepartment of Pharmacology, Miller School of Medicine, University of Miami, Miami, USA; Sylvester Comprehensive Cancer Center, University of Miami, Miami, USA; Institute for Data Science & Computing, University of Miami, Miami, USA; Corresponding authorSummary: The approval of the first kinase inhibitor, Gleevec, ushered in a paradigm shift for oncological treatment—the use of genomic data for targeted, efficacious therapies. Since then, over 48 additional small-molecule kinase inhibitors have been approved, solidifying the case for kinases as a highly druggable and attractive target class. Despite the role deregulated kinase activity plays in cancer, only 8% of the kinome has been effectively “drugged.” Moreover, 24% of the 634 human kinases are understudied. We have developed a comprehensive scoring system that utilizes differential gene expression, pathological parameters, overall survival, and mutational hotspot analysis to rank and prioritize clinically relevant kinases across 17 solid tumor cancers from The Cancer Genome Atlas. We have developed the clinical kinase index (CKI) app (http://cki.ccs.miami.edu) to facilitate interactive analysis of all kinases in each cancer. Collectively, we report that understudied kinases have potential clinical value as biomarkers or drug targets that warrant further study.http://www.sciencedirect.com/science/article/pii/S2666379120301701target validationclinical scoring systemdata integrationhuman kinomecancer drug targetunderstudied kinase |
| spellingShingle | Derek Essegian Rimpi Khurana Vasileios Stathias Stephan C. Schürer The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer Cell Reports Medicine target validation clinical scoring system data integration human kinome cancer drug target understudied kinase |
| title | The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer |
| title_full | The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer |
| title_fullStr | The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer |
| title_full_unstemmed | The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer |
| title_short | The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer |
| title_sort | clinical kinase index a method to prioritize understudied kinases as drug targets for the treatment of cancer |
| topic | target validation clinical scoring system data integration human kinome cancer drug target understudied kinase |
| url | http://www.sciencedirect.com/science/article/pii/S2666379120301701 |
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